Regulatory Requirements and Applications of Physiologically Based Pharmacokinetic Models

Publication: ADME Processes in Pharmaceutical Sciences


Physiologically based pharmacokinetic (PBPK) models have become a key tool to reduce the uncertainty and assure the best benefit-risk decisions in a model-informed drug discovery and development process. Since 1990s, PBPK simulations have been used in lieu of conducting clinical trials or have informed the prescribed information of many drugs where no other data is available to support regulatory decisions. Recognizing the need for the PBPK qualification, in order to counteract the lack of confidence of PBPK models in this field and increase the credibility, the main Regulatory Agencies such as the Food and Drug Administration and the European Medicines Agency have created some guidelines for PBPK platform qualification for an intended use as well as an evaluation of the predictive performance of the specific drug model. This chapter describes the regulatory requirements and relevance of PBPK models during drug development and regulatory review. It will be considered the role of PBPK in the regulatory field and the main regulatory guidelines as well as specific concepts related to PBPK model development and validation. The last part of the chapter includes applications of PBPK modelling and simulation for predicting the pharmacokinetic of drugs in risk assessment or pharmacokinetic exploration such as drug-drug interaction, paediatrics, organ assessment and food effect scenarios.

By Marina Cuquerella-Gilabert, Matilde Merino, Alfredo García Arieta, Victor Mangas-Sanjuan, Javier Reig López